MXPA02004787A

MXPA02004787A - Improved stannous oral compositions.

Info

Publication number: MXPA02004787A
Application number: MXPA02004787A
Authority: MX
Inventors: James White Donald Jr
Original assignee: Procter & Gamble
Priority date: 1999-11-12
Filing date: 2000-11-10
Publication date: 2002-08-30
Also published as: ES2350177T3; JP2003513899A; EP1227788A1; EP2238965A1; RU2219902C1; PL206023B1; CA2389174C; CN1420757A; AU1479301A; JP3860471B2; WO2001034108A1; RU2002115627A; HK1049611A1; PL355965A1; US20030152527A1; US6555094B1; US6821507B2; EP1227788B1; CN1200685C; ATE476955T1

Abstract

The present invention relates to oral compositions comprising a stannous ion source, a fluoride ion source, and a polymeric mineral surface active agent that binds stannous, said compositions providing adequate therapeutic efficacy with minimal side effects of tooth staining and astringency. The composition simultaneously provides reduction and control of supragingival calculus. The present oral care compositions may be formulated as single phase or dual phase compositions. The present invention also provides a method for effective delivery of stannouscontaining compositions with minimal side effects of tooth staining or astringency and with effective tartar control by administering to a subject a stable dentifrice composition comprising a clinically effective amount of stannous fluoride andor other stannous salts in combination with a fluoride ion source and a polymeric mineral surface active agent, preferably a phosphate or phosphonatecontaining polymer.

Description

IMPROVED BEAN BUCCAL COMPOSITIONS This application claims the benefit of the provisional patent application EU No. 60/165350, issued on November 12, 1999.

FIELD OF THE INVENTION The present invention relates to improved buccal compositions containing stannous salts, such as fluorine tin. These improved compositions provide a range of intra-oral benefits derived from stannous fluoride and / or other stannous salt, including antimicrobial effects, odor control, growth control of dental plaque and metabolism, reduced gingivitis, decreased progression to periodontal diseases, reductions in dentine hypersensitivity, and reduced root and crown dental caries. These improved compositions provide the aforementioned benefits with major improvements purchased with conventional compositions containing stannous, including: 1) reduced levels of tooth staining; 2) reduced astringency thus improving the aesthetic characteristics of the compositions; and 3) reduction in the formation of dental calculus. Improved compositions containing stannous provide these benefits primarily through the combined effects of stannous and polymeric mineral surface active agents, preferably including anionic polymers, such as polyphosphate or condensed polyphosphonate. The invention also discloses methods of at least maintaining therapeutic efficacy while decreasing staining and improving the aesthetic convenience of buccal compositions containing stannous salts, such as stannous fluorine.

ANTECEDENTS OF THE INVENTION Fluorine stannous is commonly known for its effectiveness when formulated in oral products. Fluorescent stannous was the first fluorine source incorporated in toothpastes for therapeutic efficacy in the control of dental caries. Fluorescent stannous gel, rinses, and dentifrices have been shown to provide clinical efficacy for the reduction of dental caries, dentine hypersensitivity, dental plaque, and gingivitis. In addition to these clinical effects, formulations containing stannous fluoride can also help provide improved breath benefits through chemical and antibacterial actions. Fluorine stannous formulations typically include stabilization systems designed to maintain levels of bioavailability (ie, soluble and reactive) of the stannous during shelf storage, explaining the loss of stannous to oxidation or precipitation. Therefore, the stannous fluoride formulations may contain other additional ingredients containing stannous, which can provide important stabilization benefits to achieve efficacy. The high stannous concentrations in dental formulations help to assure the stability of the stannous fluoride and therefore the clinical efficacy of the formulations containing the latter. Unfortunately, although it is known that stannous fluoride compositions are highly effective, successful commercial use is complicated by the complexity in the development of formulations that provide adequate stannous fluoride stability and in the side effects of stannous. Formulations that provide increased or improved efficacy typically stimulate increased side effects. This limits the clinical and commercial applications. One of the most notable side effects of regular use of stannous fluoride is yellow-brown tooth staining. This stain is derived from the film, plaque and reactions of food compounds with the available stannous deposited on the surfaces of the teeth during treatment with effective formulations of stannous fluoride. A second side effect found routinely during the use of effective formulations of stannous fluoride is unacceptable formulation astringency. Precipitants are applied locally to astringents whose low cell permeability restricts actions to cell surfaces and intersitial spaces. Strong astringents can induce contraction and wrinkling of tissues and can precipitate or reduce mucous secretions. Inside the mouth products, these chemical actions produce an unpleasant sensation "of dryness" in the oral cavity, such as in the tongue, gingival tissues or oral epithelium. Stannous formulations that contain sufficient stannous for bioavailability are routinely described as astringent by patents and consumers and this property is undesirable. The astringency is more noticeable after the use of the product. A third side effect of the regular use of fluoride stannous dentifrice compositions is the decreased efficacy in reducing dental calculus with these compositions. The present inventors have established that the proven effectiveness of fluoride stannous dentifrices for antimicrobial, antigingivitis and other expected benefits does not always show reproducible clinical actions towards preventing the accumulation of undesirable supragingival dental calculus. The control of supragingival calculus formation along with other clinical benefits is desired by professionals, patients and consumers. The multifunctional activity of oral compositions can simplify hygiene and provide a holistic approach to maintaining therapeutic oral health. Previous attempts to develop oral compositions of stannous fluoride acceptable to the consumer have tried to solve these cumulative damages, however none has been totally successful. US Patent 5,004,597, issued to Majeti et al., Describes buccal compositions containing stannous fluoride and gluconate salts. The inclusion of stannous gluconate results in improved formulation stability and efficacy. While effective, this formulation produces unwanted levels of tooth staining. In addition, the formulation had an unacceptable aesthetics, derived mainly from the astringency of the stannous. Also, US Patent 5,578,293, issued to Prencipe et al., Describes the use of an organic acid compound to stabilize the concentration of stannous ion. Coupled with stannous fluoride and citrate as the organic acid, the formulation also includes soluble salts of pyrophosphate. US Patent 4,323,551 to Parran et al., Discloses the use of pyrophosphate salts to provide anticalculus benefits. Clinical research has established the potential of active anionic mineral surface inhibitors, such as pyrophosphates, by preventing the development of natural and antimicrobial induced tooth staining (Grossman, Bolimer, Sturzenberger and Vick; Journal of Clinical Dentistry 6 (4): 185-187, 1995). In the Prencipe et al. Patent, all examples include a sufficient amount of citric acid and / or sodium citrate dihydrate to stabilize the stannous ions and prevent precipitation. These levels also directly inhibit the binding of the stannous with pyrophosphate salts. If the stannous did not bind pyrophosphate salts, studies argue that this would reduce the antimicrobial activity of stannous fluoride. The level of citrate necessary to effectively stabilize the stannous against precipitation and the pyrophosphate, the union would also detract from the aesthetic value of the stannous composition. The composition will be salty, acidic, and the stannous linked to the citrate will still act as an astringent, which reduces all taste acceptability. US Patent 5,213,790, issued to Lukacovic et al., Also discloses the use of a citrate ion source in a stannous composition. US Patent 5,780,015, issued to Fisher et al., Discloses the use of dual phase toothpaste containing a potassium salt and a stannous salt whereby the hydrogenated castoreum oil is used to help reduce astringency. The stannous salt is stabilized by the use of an organic acid compound as described in Prencipe et al. Another attempt to produce an effective stannous composition is described in U.S. Patent 5,716,600, issued to Zhrandik et al. This patent describes low water formulations that help prevent the stagnant fluoride from degrading over time. No attempts have been made to reduce the staining of the formulation. US Patent 5,017,363, issued to Suhonen, discloses a stannous iron chelating copolymer of an alkyl vinyl ether and anhydride or maleic acid in an amount to effectively stabilize the stannous ions. Suhonen also discloses that the compositions are substantially free of silica, soluble phosphates such as soluble pyrophosphates (e.g., tetrasodium pyrophosphate and tetrapotassium pyrophosphate), and the aldehyde group containing compounds, since the stabilizing function of the ion chelating polymer Stagnant is not effective in the presence of these ingredients. US Patent 5,338,537, issued to White, Jr., et al., Discloses the use of a low molecular weight diphosphonic acid, which is used as a binding agent for the stannous in order to help reduce the tendency of staining to from the composition. While it is effective in reducing the potential for staining, laboratory studies have shown that the antibacterial activity of complex stannous containing formulations with low molecular weight diphosphonic acid is very low. Similar results have been obtained in formulations with soluble salts of pyrophosphate, in the absence of solid citrate chelation, as described above. Based on the above, it appears that the same chemical and biochemical binding sites can be involved for both antibacterial / antiplaque activities and for stabilization and to reduce the staining potential of stannous fluoride. Thus, in order to achieve stabilization and / or reduction of tooth staining, antibacterial / antiplaque activity can be endangered. This hinders the optimal development of stannous fluoride oral compositions and explains the limited number of stannous fluoride compositions on the market today. To improve consumer acceptance and compliance with the use of oral compositions containing stannous, a stannous composition is needed which is highly effective but with a low level of staining and other negative aesthetics, such as astringency. Furthermore, it is desirable that these formulations provide simultaneous efficacy towards the reduction and control of dental calculus formation.

BRIEF DESCRIPTION OF THE INVENTION The present invention describes buccal compositions containing a source of stannous ion, a fluorine ion source, and a polymeric mineral surface active agent that binds stannous, said compositions provide adequate therapeutic efficacy with minimal side effects of tooth staining. and astringency. The compositions simultaneously provide reduction and control of supragingival calculi. Current oral care compositions can be formulated as one-phase or dual-phase compositions. The present invention also provides a method for the effective delivery of stannous containing compositions with minimal side effects of tooth staining or astringency and effective tartar control by administering to a subject a stable dentifrice composition comprising a clinically effective amount of stannous fluorine. and / or other stannous salts in combination with a polymeric mineral surface active agent, preferably a phosphate or phosphonate-containing polymer. These and other features, aspects and advantages of the present invention will become apparent to those skilled in the art from the detailed description.

DETAILED DESCRIPTION OF THE INVENTION While the specification concludes with claims that particularly indicate and clearly claim the invention, it is considered that the present invention will be better understood from the following description. All percentages used herein are by weight of the dentifrice composition, unless otherwise specified. The relationships used herein are molar ratios of the total composition, unless otherwise specified. All measurements are made at 25 ° C, unless otherwise specified. In the present, "comprises" means that other steps and other ingredients may be added that do not affect the final result. This term includes the terms "consisting of" and "consisting essentially of". The buccal composition of the present invention may be in the form of a toothpaste, toothpaste, paste powder, topical oral gel, mouthwash, dental product, mouthwash, lozenge, oral tablet or chewing gum. The term "dentifrice", as used herein, means paste, gel or liquid formulations unless otherwise specified. The dentifrice composition can be in any desired form, such as deep listing, listing surface, multiple layers, with the gel surrounding the paste, or any combination thereof. If a dual-phase buccal composition is desired, each buccal composition will be contained in a physically separate compartment of a delivery device and side by side of delivery. The term "delivery device" used herein means any suitable pump, tube or container for supplying toothpaste. The buccal composition may be a one-phase buccal composition or may be a combination of two or more buccal compositions. The oral composition is a product, which in the ordinary course of administration, is not intentionally swallowed for purposes of 0 systemic administration of particular therapeutic agents, but rather is retained in the buccal cavity for a sufficient time to substantially contact all the surfaces of the teeth and / or buccal tissues for purposes of buccal activity. The term "total composition" as used in the present invention means the total composition delivered to the buccal cavity, regardless of whether it contains a single phase or multiple phases. The term "aqueous vehicle" as used herein means any safe and effective material for use in the compositions of the present invention. Such materials include tartar control agents, antibacterial agents, glossy abrasive materials, peroxide sources, alkali metal bicarbonate salts, thickeners, humectants, water, pH regulating agents, surfactants, titanium dioxide, flavoring system, sweetening agents, coloring agents, and mixtures thereof. In the present, the term "tartar" and "calculus" are used interchangeably and refer to mineralized dental plaque biofilms. The term "stannous" as used herein, is defined to mean the stannous which is a dentifrice or other oral product, and is supplied by a source such as stannous salts including stannous fluorine. It can refer to the stannous ions that are provided by a stannous salt different from the stannous fluorine, added for stabilization purposes.

The present invention describes buccal compositions comprising a source of stannous ion, a source of fluorine ion, and a polymeric mineral surface active agent that binds the stannous, said compositions provide adequate therapeutic efficacy with minimal side effects of tooth staining and astringency. The compositions simultaneously provide reduction and control of supragingival calculi. The aesthetic and astringency benefits of the stannous combination and polymeric mineral surface active agents are enhanced by the appropriate concurrent formulation, including the use of appropriate poloxamer ingredients. The polymeric mineral surface active agent is preferably a polyphosphate having an average chain length of about 4 or more, a polyphosphonate, or other anionic phosphate or phosphonate-containing polymers. The person skilled in the art can assume that a polymeric binding agent, such as a polyphosphate with an average chain length of about 4 or more, would behave in a manner similar to pyrophosphate or tripol phosphate in the stannous containing dentifrice systems. . The present invention has discovered that the chemical binding of the stannous using pyrophosphate, diphosphonate, or tripol phosphate to prevent spotting, also produces unacceptable losses in therapeutic potential. However, an unexpected result occurs with the polyphosphate present and other phosphate or phosphonate-containing polymers since they have the ability to reduce the side effects of dental staining and formulation astringency without significantly reducing the efficacy of the stannous. The present inventors have in fact discovered that by including these polymeric mineral surface active agents in buccal compositions containing stannous salts such as stannous fluorine, they provide important therapeutic efficacy with reduced levels of staining and astringency, while simultaneously providing reductions in supragingival stones in comparison with prior art compositions containing stannous fluorine alone or stannous fluorine with stabilizing agents such as citrates. The present oral care compositions can be formulated as one-phase or dual-phase compositions. One embodiment of the present invention provides a dual phase oral composition comprising a first composition comprising a fluorine ion source and a source of stannous ion and a second composition comprising a linear polyphosphate having an average chain length of about 4 or more, whereby the second composition has a total water content of up to about 20%. A further embodiment of the present invention describes a one-phase buccal composition comprising a fluorine ion source, a source of stannous ion and a linear polyphosphate having an average chain length of about 4 or more, so that the linear polyphosphate is stabilized against hydrolytic degradation.

The present invention also discloses one phase or dual phase compositions comprising a fluorine ion source, a source of stannous ion and an anionic polymer of MW 500 or more containing functionalities of phosphonic acid or diphosphonic acid, alone or in combination with carboxylate functionalities, so that the oral composition provides adequate therapeutic efficacy with minimal side effects of tooth staining and astringency while simultaneously providing reductions in cosmetic supragingival calculi. The invention also provides a method for the effective delivery of compositions containing stannous with minimal side effects of tooth staining or astringency and effective tartar control by administering to a subject a stable dentifrice composition comprising a clinically effective amount of stannous fluoride and / or other stannous salts in combination with a polymeric mineral surface active agent, such as a phosphate polymer or containing phosphonate. One method for the delivery of this improved stannous buccal composition includes the application of a dentifrice comprising two dentifrice compositions that are contained in physically separate compartments. Another method includes administering to a subject a stable, one-phase dentifrice composition. An embodiment of a stable one-phase composition comprises a polyphosphate, or other anionic phosphate-containing phosphonate polymer; a stannous source supplied from a source other than stannous fluorine; and a source of fluorine, so that the composition may have a limited total water content, depending on the stability requirements. A preferred method for delivery of the present improved compositions containing stannous includes the application of a dentifrice comprising two dentifrice compositions which are contained in physically separate compartments. The physical separation allows an adequate stabilization of each tooth phase and ingredients in it. When combined in use, the chemical interactions of the stannous (from stannous fluoride and / or other stannous salts) in a dentifrice phase with the polymeric binding agent in a separate dentifrice phase allows the proper supply of both ingredients, thus producing activity total therapeutic together with the provision of significant efficacy for the reduction of dental calculus and with marked reductions in the unwanted side effects of tooth staining and astringency. The first dentifrice composition comprises a polyphosphate, or other anionic phosphate or polymers containing phosphonate and may have a limited total water content, while the composition of the second phase comprises stannous ions, The present compositions comprise essential compounds, as well as optional compounds . The essential and optional compounds of the compositions of the present invention are described in the following paragraphs: Sources of stannous ion The present invention includes a source of stannous ion as an essential compound. The stannous ions are supplied with stannous fluoride and / or other stannous salts that are added to the buccal composition. It has been discovered that stagnant fluoride helps in caries reduction, gingivitis, plaque, sensitivity, and improved breath benefits. The stannous provided in the buccal composition will provide efficacy to a subject using the composition. Other stannous salts include stannous chloride dihydrate, stannous acetate, stannous gluconate, stannous oxalate, stannous sulfate, stannous lactate, and stannous tartrate. The preferred sources of stannous ion are stannous fluorine and stannous chloride dihydrate. The combined stannous salts will be present in an amount of from about 0.1% to about 11% by weight of the total composition. Preferably, the stannous salts are present in an amount of from about 0.5 to about 7%, more preferably from about 1% to about 5%, and most preferably from about 1.5% to about 3% by weight of the total composition . Efficacy-providing formulations typically include stannous levels, provided by stannous fluoride and stannous stabilizing salts, ranging from about 3,000 ppm to about 15,000 ppm of stannous ions in the total composition. Below 3,000 ppm of stannous the efficiency of the stannous is not enough. Preferably, the stannous ion is present in an amount of from about 4,000 ppm to about 12,000 ppm, more preferably from 5,000 ppm to about 10,000 ppm. Dentifrices containing stannous salts, particularly stannous fluoride and stannous chloride, are described in US Pat. No. 5,004,597 to Majeti et al., Incorporated herein in their entirety. Other descriptions of stannous salts are found in US Patent 5,578,293, issued to Prencipe et al., And US Patent 5,281,410 issued to Lukacovic et al., Incorporated herein in their entirety. In addition to the source of stannous ion, other ingredients necessary to stabilize the stannous can also be included, such as the ingredients described in Majeti et al., And Prencipe et al.

Fluorine ion sources The buccal compositions of the present invention will include as a second essential component a source of soluble fluorine with the ability to provide bioavailability and effective fluorine ions. Soluble fluorine ion sources include sodium fluorine, stannous fluorine, indium fluorine, and sodium monofluorophosphate. Fluorine stannous is the most preferred source of soluble fluorine. This ingredient can serve as a stannous source and source of fluorine. Norris et al., U.S. Patent 2,946,725, issued July 26, 1960, and Widder et al., U.S. Patent 3,36,778,154 issued July 18, 1972, describe said sources of fluorine as well as others. Both patents are hereby incorporated by reference in their entirety.

The present compositions may contain a source of soluble fluorine ion with the ability to provide from about 50 ppm to about 3500 ppm, and preferably from about 500 ppm to about 3000 ppm of free fluorine ions. To supply the desired amount of fluorine ions, the fluorine ion sources may be present in the total buccal composition in an amount of from about 0.1% to about 5%, preferably from about 0.2% to about 1%, and with greater preference of about 0.3% to about 0.6%, by weight of the total composition delivered to the buccal cavity.

Active polymeric mineral surface active agent The present invention includes a polymer surface active agent (MSA). These agents show affinity for stannous binding, in particular by chelating stannous ion, as evidenced by the release of fluorine from stannous fluorine. (SnF2) and provision of increased ionic form of fluorine to the binding of the stannous. Effective agents also show surface reactivity towards calcium phosphate minerals, and this is expected to slow the formation of calculus or tartar. Agents can also provide spot control and surface conditioning. These agents will bind the stannous but will still allow the combined mixture to provide the desired control of scale, stain control, and surface conditioning, without having a negative effect on the efficacy of stannous fluoride for the control of dental caries, bad breath and diseases. periodontal diseases including gingivitis. The present active agents of polymeric mineral surface will solidly bind the stannous and will retain the biological reactivity while inhibiting the undesirable staining. Research has shown that binding generally occurs in the final functions of condensed phosphate polymers. The linkage can differ from other phosphate polymers or effective phosphonate or co-polymers. Therefore, a mineral surface active agent with final phosphate groups that provide the predominant binding is preferred. Even more preferred are the mineral surface active agents that have one or more internal phosphate groups in addition to the phosphate end groups. The polymeric mineral surface active agents that are useful in the present invention include polyelectrolytes such as condensed phosphorylated polymers; polyphosphonates; copolymers of phosphate monomers or containing phosphonate or polymers with other monomers such as ethylenically unsaturated monomers and amino acids or with other polymers such as proteins, polypeptides, polysaccharides, poly / acrylate), poly (acrylamide), poly (me acrylate) , poly (ethacrylate), poly (hydroxyalkyl methacrylate), poly (vinyl alcohol), poly (maleic anhydride), poly (maleate), poly (amide), poly (ethyleneamine), poly (ethylene glycol), poly (propylene glycol), poly ( vinyl acetate), and poly / vinylbenzylchloride); carboxy-substituted polymers; and mixtures thereof. Polymer surface active agents include the carboxy-substituted alcohol polymers described in US Patents 5,292,501, 5,213,789, 5,093,170; 5,009,882; and 4,939,284; all to Degenhardt et al., and the diphosphonate-derived polymers in US Patent 5,011, 913 to Benedict et al. Suitable structures include copolymers of acrylic acid or methacrylic acid with phosphonates. A preferred polymer is the modified polyacrylic acid disphosphonate. Suitable phosphonate-containing polymers such as those shown below are described in U.S. Patent 5,980,776 to Zakikhani, et al., Incorporated herein in their entirety. 1. Copolymer of acrylic acid and diphosphonic acid with structure: 2. Copolymer of acrylic acid and vinylphosphonic acid with structure: 3. Copolymer of methacrylic acid and vinylphosphonic acid with structure: 4. Copolymer of acrylic acid and vinyl diphosphonic acid with structure: A preferred polymeric mineral surface active agent will be stable with fluorine and will not hydrolyze in high water content formulations, thereby allowing a single phase single dentifrice or mouth rinse formulation. If the polymeric mineral surface active agent does not have these stability properties, it is very likely that a dual phase formulation with the polymeric mineral surface active agent separated from the fluorine source is required. A preferred polymeric mineral surface active agent is a polyphosphate. It is generally understood that a polyphosphate consists of two or more phosphate molecules arranged mainly in a linear configuration, although some cyclic derivatives may be present. Although pyrophosphates and tripolyphosphates are technically polyphosphates, the desired polyphosphates are those that have about four or more phosphate molecules so that adsorption of the surface at effective concentrations produces sufficient unbound phosphate functions that improve the surface charge. anionic as well as the hydrophilic character of the surfaces. The pyrophosphates are analyzed separately under additional anticalculus agents. The desired inorganic polyphosphate salts include tetrapolyphosphate and hexametaphosphate, among others. Polyphosphates larger than tetrapolyphosphates generally occur as amorphous glassy materials. In this embodiment, the "glassy" polyphosphates are preferred with the formula: XO (XPO3) nX wherein X is sodium or potassium and n ranges from about 6 to about 125. Polyphosphates manufactured by FMC Corporation which are commercially known as Sodaphos are preferred ( n »6), Hexaphos (n« 13), and Glass H (n «21). The most preferred polyphosphate is glass H. These polyphosphates can be used alone or in a combination thereof. It is also known that polyphosphates with an average chain length greater than about 4 will react with ionic fluoride in mouth compositions at room temperature and will produce monofluorophosphate ions, in addition to altering the pH of the composition. This reaction jeopardizes the efficacy of the oral composition and its ability to provide stable ionic fluoride and polyphosphates to the oral surfaces. It is also known that in order to have stable polyphosphates, the total water content of the dentifrice composition must be controlled to reduce hydrolysis of the polyphosphate. US Patent 5,939,052 issued to White, Jr. et al., Incorporated herein by reference in its entirety, further discloses polyphosphates. Phosphate sources are also described in greater detail in Kirk-Othmer Encyclopedia of Chemical Technology, 4th Edition, VOLUME 18, Wiley-Interscience Publishers (1996), incorporated herein by reference in its entirety, including all references incorporated in Kirk. -Othmer.

The amount of mineral surface agent required is an effective amount that will bind the stannous, allow adequate antimicrobial activity, reduce dental stains and formulation astringency, and have the ability to reduce dental calculus. An effective amount of a mineral surface active agent will typically be from about 1% to about 355, preferably from about 2% to about 30%, more preferably from about 5% to about 25%, and most preferably from about 6% to about 20%, by weight of the total oral composition. A sufficient amount of mineral surface active agent, fluorine ions and stannous ions must be present for the composition to be effective. When formulating phosphate-containing compositions, the total molar ratio of phosphate anon with the total moles of stannous ion should also be controlled. For condensed phosphates with an average of 21 phosphate repeating units, it has been found that the ideal molar ratio is a molar ratio of phosphate anion with stannous ion of about 0.2: 1 to about 5: 1, preferably about 0.5: 1 to about 3: 1, more preferably from about 0.6: 1 to about 2: 1, and most preferably from about 0.7: 1 to about 1: 1. In tion to binding stannous ions effectively, it has been found that the polymeric mineral surface active agent solubilizes the insoluble salts. For example, it has been found that glass phosphate H solubilizes the insoluble stannous salts as well as oxides and stannous hydroxides.

Aqueous vehicles When preparing the present compositions, it is desirable to add one or more aqueous vehicles to the compositions. Such materials are well known in the art and are easily chosen by the person skilled in the art based on the desired physical and aesthetic properties for the compositions to be prepared. These aqueous vehicles can be included at levels that do not prevent the interaction between the stannous and the polymeric mineral surface active agent. The amounts of polymeric, stannous, and fluorine mineral surface active agent can be adjusted if necessary to compensate for additional vehicles. Aqueous vehicles typically comprise from about 50% to about 99%, preferably from about 70% to about 98%, and more preferably from about 90% to about 95% by weight of the buccal composition.

Total water content The water used in the preparation of commercially appropriate oral compositions should preferably be low in ion content and free of organic impurities. In the buccal composition, the water will generally comprise from about 5% to about 95%, and preferably from about 10% to about 50%, by weight of the composition in the present invention. This water content can be in a one-phase buccal composition or it can be the total water content resulting from a dual-phase buccal composition. If the buccal composition comprises a polyphosphate having an average chain length of about 4 or more, the composition or phase containing the polyphosphate will comprise a lower level of water, generally up to about 20% total water. Preferably, the total water content is from about 2% to about 20%, more preferably from about 4% to about 15%, and most preferably from about 5% to about 12%, by weight of the oral composition . The amounts of water include the free water that is added in addition to that which is introduced with other materials, such as sorbitol, silica, surfactant solutions, and / or color solutions.

PH regulating agent The present compositions may contain a pH regulating agent. The pH regulating agents, as used in the present invention, refer to agents that can be used to adjust the pH of the compositions at a scale from about pH 3.0 to about pH 10. The phase of the oral composition containing Stannous will typically have a slurry pH of about 3.0 to about 7.0, preferably about 3.25 to about 6.0, and more preferably about 3.5 to about 5.5. The phase containing the polymeric mineral surface active agent will typically have a slurry pH of about 4.0 to about 10, preferably about 4.5 to about 8, and more preferably about 5.0 to about 7.0. A buccal composition containing stannous and polymeric mineral surface active agent in one phase will typically have a pH of from about 4 to about 7, preferably from about 4.5 to about 6.5, and more preferably from about 5 to about 6. pH regulating agents include alkali metal hydroxides, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazole and mixtures thereof. Specific pH regulating agents include monosodium phosphate, trisodium phosphate, sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, alkali metal carbonate salts, sodium carbonate, imidazole, pyrophosphate salts, citric acid, and sodium citrate. The preferred pH regulators will be those that control the pH on the target scale without complex stannous ions. Preferred pH regulating agents include acetic acid, sodium acetate, citric acid, sodium citrate, benzoic acid and sodium benzoate. The pH regulating agents are used at a level of from about 0.1% to about 30%, preferably from about 1% to about 10%, and more preferably from about 1.5% to about 3%, by weight of the composition I presented.

Additional anticalculus agents The optional agents to be used in combination with the stannous fluoride which binds the polymeric mineral surface active agent include said materials known to be effective in reducing the mineral deposit related to stone formation. These agents may be included at levels that do not prevent the formation of the stannous fluoride that binds the complex mineral surface active agent. The included agents are pyrophosphates, tripolyphosphates, and synthetic anionic polymers including polyacrylates and copolymers of anhydride or maleic acid and methyl vinyl ether, such as Gantrez as described in US Patent 4,627,977 to Gaffar et al., And polyaminopropane sulfonic acid (AMPS) ) Also included are zinc citrate trihydrate, diphosphonates such as EHDP and AHP and polypeptides such as polyaspartic and polyglutamic acids, and mixtures thereof.

Abrasive gloss materials A glossy abrasive material may also be included in the buccal compositions. The gloss abrasive material for use in the compositions of the present invention can be any material that does not excessively wear dentin. Additionally, the gloss abrasive material should be formulated in the buccal composition so that it does not compromise the stability of the stannous fluoride. For example, in a dual-phase buccal composition, the gloss abrasive material is preferably in a separate phase from the fluorine ion source and the stannous ion source.

Typical gloss abrasive materials include silicas that encompass gel, precipitates; aluminas; phosphates including orthophosphates, polymetaphosphates, and pyrophosphates; and mixtures thereof. Specific examples include dicalcium dihydrate orthophosphate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, beta calcium pyrophosphate, calcium carbonate, and resinous abrasive materials such as condensation products of urea particles. and formaldehyde, and others such as those described by Cooley et al., in US Patent 3,070,510, issued December 25, 1962, incorporated herein by reference. Mixtures of abrasives can also be used. If the buccal composition or particular phase comprises a polyphosphate having an average chain length of about 4 or more, the abrasives containing calcium and alumina are not preferred abrasives. The most preferred abrasive is silica. Silica dental abrasives of various types are preferred because of their unique benefits of cleaning performance and exceptional tooth shine without excessively abrading tooth enamel or dentin. The silica gloss abrasive materials in the present invention, as well as other abrasives, generally have an average particle size ranging from about 0.1 to about 30 microns, and preferably from about 5 to about 15 microns. The abrasive can be precipitated silica or silica gel such as silica xerogel marketed under the trademark "Syloid" by W. R. Grace & Company, Davison Chemical Division. Also preferred are precipitated silica materials such as those marketed by J: M: Huber Corporation under the trademark "Zeodent", particularly the silica bearing the designation "Zeodent 119". The types of dental silica abrasives useful in toothpastes of the present invention are described in greater detail in Wason, US Patent 4,340,5583, issued July 29, 1982, incorporated herein by reference. Silica abrasives are also described in Rice, US Patent 5,589,160; 5,603,920; 5,651, 958; 5,658,553; and 5,716,601; incorporated herein by reference. The abrasive in the buccal compositions described herein is generally present at a level of from about 6% to about 70% by weight of the composition. Preferably, the buccal compositions contain from about 10% to about 50% abrasive, by weight of the buccal composition.

Peroxide Source The present invention may include a peroxide source in the composition. The source of peroxide is selected from the group consisting of hydrogen peroxide, calcium peroxide, urea peroxide, and mixtures thereof. The preferred peroxide source is calcium peroxide. Preferably, to maximize stability, the peroxide source is not in the same phase as the source of stannous ion. The following amounts represent the amount of peroxide feedstock, although the peroxide feedstock may contain ingredients other than peroxide feedstock. The present composition may contain from about 0.01% to about 10%, preferably from about 0.1% to about 5%, more preferably from about 0.2% to about 3%, and most preferably from about 0.3% to about 0.8 % of a peroxide source, by weight of the oral composition.

Alkali metal bicarbonate salts The present invention may also include a bicarbonate salt of alkali metal. Alkali metal bicarbonate salts are water soluble and unless stabilized, they tend to release carbon dioxide in an aqueous system. Sodium bicarbonate is the preferred alkali metal bicarbonate salt. This alkali metal bicarbonate salt also functions as a pH regulating agent. Because the pH at which the alkali metal bicarbonate salts regulate the pH, it is preferable that the bicarbonate salt be in a separate phase from the stannous source. The present composition may contain from about 0.5% to about 50%, preferably from about 0.5% to about 30%, more preferably from about 2% to about 20%, and most preferably from about 5% to about 18%. % of a bicarbonate salt of alkali metal, by weight of the buccal composition.

Additional Aqueous Vehicles The compositions of the present invention are in the form of toothpastes, dentifrices, topical mouth gel, mouthwash, dental products, mouth spray, lozenges, oral tablets or chewing gums and typically contain some thickener or binder material to provide a desirable consistency. The amount and type of the thickening material will depend on the shape of the product. Preferred thickening agents are carboxyvinylpolymers, carrageenan, hydroxyethylcellulose, and water-soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium hydroxyethylcellulose. Natural gums such as karaya gum, xanthan gum, gum arabic, and tragacanth gum can also be used. The aluminum silica of colloidal magnesium or finely divided silica can also be used in an amount of from about 0.1% to about 15%, by weight of the buccal composition. Another optional compound of the compositions desired herein is a humectant. The humectant serves to prevent the oral composition from hardening when exposed to air and certain humectants may also provide the desired sweetness of flavor to the toothpaste compositions. Suitable humectants for use in the invention include glycerin, sorbitol, polyethylene glycol, propylene glycol, xylitol, and other edible polyhydric alcohols. The humectant generally comprises from about 0% to 70%, and preferably from about 15% to 55%, by weight of the oral composition.

The present compositions may also include surfactants, commonly referred to as foaming agents. Suitable surfactants are those that are reasonably stable and foam throughout a broad pH range. The surfactant may be anionic, nonionic, amphoteric, switerionic, cationic or mixtures thereof. Surfactants useful in the present invention include the water-soluble salts of alkyl sulfates having from 8 to 20 carbon atoms in the alkyl radical (e.g., sodium alkyl sulphate) and the water-soluble salts of sulfonated monoglycerides of fatty acids having from 8 to 20 carbon atoms. Sodium lauryl sulfate and sodium coconut monoglyceride sulfonates are examples of anionic surfactants of this type. Other suitable anionic surfactants are sarcosinates, such as sodium lauryl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauryl sethionate, sodium lauretcarboxylate, and sodium dodecylbenzene sulfonate. Mixtures of anionic surfactants can also be used. Many suitable anionic surfactants are described by Agricola et al., US Patent 3,959,458, issued May 25, 1976, incorporated herein by reference in its entirety. The nonionic surfactants that can be used in the compositions of the present invention can be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which can be aliphatic or alkylaromatic in nature. . Examples of suitable nonionic surfactants include poloxamers (sold under the tradename Pluronic), polyoxyethylene, polyoxyethylene sorbitan esters (sold under the trademark Tweens), hydrogenated castor oil Polyoxyl 40, fatty alcohols ethoxylates, polyethylene oxide condensates of alkylphenols , products derived from the condensation of ethylene oxides with the reaction product of propylene oxide and ethylenediamine, condensates of ethylene oxide of aliphatic alcohols, long chain tertiary amino oxides, phosphino long chain tertiary oxides, long chain dialkylsulfoxides and mixtures of said materials. Poloxamer 407 nonionic surfactant is one of the most preferred surfactants because it has been found that the poloxamer helps reduce the astringency of the stannous. Amphoteric surfactants useful in the present invention can be broadly described as secondary and tertiary aliphatic amine derivatives in which the aliphatic radical can be a straight or branched chain and whereby one of the aliphatic substituent atoms contains from about 8 to about 18 carbon atoms and one contains an anionic hydroperoxide group, for example, carboxylate, sulfonate, sulfate, phosphate, or phosphonate. Other suitable surfactants are betaines, specifically cocomidopropyl betaine. Mixtures of amphoteric surfactants can also be used. Many of the appropriate non-ionic and amphoteric surfactants are described by Gieske et al., US Patent 4,051, 234, issued September 27, 1977, incorporated herein by reference in its entirety. The present composition typically comprises one or more surfactants each at a level of from about 0.25% to about 12%, preferably from about 0.5% to about 8%, and most preferably from about 1% to about 6%, in Weight of the tooth composition. Titanium dioxide can also be added to the present composition. The coloring agent can be in the form of an aqueous solution, preferably 1% of coloring agent in a water solution. The color solutions generally comprise from about 0.01% to about 5%, by weight of the composition. A flavoring system can also be added to the compositions. Suitable flavoring compounds include wintergreen essence, peppermint oil, spearmint oil, clove bud oil, menthol, anethole, methylsalicylate, eucalyptol, cassia, 1-methylacetate, sage, eugenol, parsley oil, oxanone, alpha- irisone, marjoram, lemon, orange, propenilguaetol, cinnamon, vanillin, ethylvanillin, heliotropin, 4-cis-heptenal, diacetyl, methyl-para-tert-butyl phenylacetate, and mixtures thereof. The dyes can also be part of the flavoring system. The preferred colorants in the present compositions are the carboxyamide paramentan, such as N-ethyl-p-menthane-3-carboxamide (commercially known as "WS-3") and mixtures thereof. A flavoring system is generally used in the compositions at levels of from about 0.001% to about 5%, by weight of the composition.

Sweetening agents can be added to the compositions. These include saccharin, dextrose, sucrose, lactose, xylitol, maltose, levulose, aspartame, sodium cyclamate, D-tryptophan, dihydrochalcones, acesulfame, and mixtures thereof. Various coloring agents may also be incorporated in the present invention. Sweetening agents and coloring agents are generally used in toothpastes at levels of about 0.005% or about 5%, by weight of the composition. The present invention also includes other agents in addition to the estanosa to provide antimicrobial benefits. These agents can be included at levels that do not prevent the interaction between the stannous and the polymeric mineral surface active agent. Such antimicrobial agents include water-soluble non-cationic antimicrobial agents such as diphenyl halogenated ethers, phenyl compounds including phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic and halogenated salicylanilide compounds, benzoic esters, and carbanilides. halogenated Water-soluble antimicrobials include quaternary ammonium salts and bis-bicuanide salts, among others. Triciosan monophosphate is an additional water-soluble antimicrobial agent. Quaternary ammonium agents include those in which one or more of the substitutes in the quaternary nitrogen has a carbon chain length (typically alkyl group) of from about 8 to about 20, typically from about 10 to about 18 carbon atoms. carbon while the remaining substitutes (typically alkyl or benzyl group) have a lower number of carbon atoms, such as from about 1 to about 7 carbon atoms, typically methyl or ethyl groups. Ammonium dodecyltrimethyl bromide, tetradecylpyridinium chloride, domiphene bromide, N-tetradecyl-4-ethyl pyridinium chloride, dodecyldimethyl (2-phenoxyethyl) ammonium bromide, benzyl dimethyl stearyl ammonium chloride, cetylpyridinium chloride, hexahydropyrimidine 5-amino-1, 3-bis (2-ethylhexyl) -5-methyl quatemized, benzalkonium chloride, benzethonium chloride, and methylbenzethonium chloride are exemplary of typical quaternary ammonium antibacterial agents. Other compounds are bis (4- (r-amino) -1-pyridinium) alkanes as described in US Pat. No. 4,206,215, issued June 3, 1980, to Balley, incorporated herein by reference. Other antimicrobials may also be included such as copper bisglycinate, copper glycinate, zinc citrate and zinc lactate. Enzymes, including endoglycosidase, papain, dextranase, mutanase, and mixtures thereof, are also useful. Such agents are described in US Patent 2,946,725, July 26, 1960, to Norris et al., And US Patent 4,051, 234, to Gieske, et al., Incorporated herein by reference. Specific antimicrobial agents include chlorhexidine, triclosan, triclosanmonophosphate, and flavor oils such as thymol. Triclosan and other agents of this type are described in U.S. Patent 5,015,466, issued to Parran, Jr., et al., And U.S. Patent 4,894,220 to Nabi, et al., Incorporated herein by reference. Water-soluble antimicrobial agents, water-soluble agents, and enzymes may be present in the first and second buccal compositions If there are two phases. These agents may be present at levels of from about 0.01% to about 1.5%, by weight of the oral composition. A dentifrice composition can be a paste, gel, or any configuration or combination thereof. If a dual-phase dentifrice is desired, the first and second dentifrice compositions will be physically separated in a dentifrice delivery device. It is generally preferred that the first dentifrice composition be a paste and the second dentifrice composition be a gel. The delivery device may be a tube, pump, or any other suitable container for supplying toothpaste. The dual compartment packages suitable for this purpose are described in the US patent 4,528,180; US Patent 4,687,663; and 4,849,213, all to Shaeffer, all incorporated herein in their entirety. The device will provide approximately equal amounts of each dentifrice composition through an opening. The compositions can be intermixed once supplied. Alternatively, the buccal formulation can be supplied as a kit containing two separate delivery devices that are used to deliver two dentifrice compositions that are used simultaneously.

Efficiency Measures The entire performance of the present compositions can be defined in terms of a spot score / efficacy score ratio, whereby the efficiency is measured using the in-vitro plate and regrowth glycolysis model (i-PGRM). ), and the stain is measured using the in-vitro film tea stain model (i-PTSM). The present compositions provide an efficacy score at a stain score ratio of at least 1.2, which represents a realistic improvement by maintaining sufficient therapeutic efficacy while achieving a reduction in staining. The improvement in formulation astringency is defined as greater than 50% of the increase in mouth feel parameters of formulation such as mouth be, and clean mouth indices as defined in consumer controlled tests. The effectiveness for supragingival calculus control is defined by the activity in the prevention of plaque calcification using the modified plaque growth and mineralization assay.

Antimicrobial activity The concentration of stannous ion and bioavailability required for the provision of therapeutic actions may differ for different clinical actions, for example, caries vs. gingivitis. However, it is of vital importance to establish a minimum level of antimicrobial activity, since the therapeutic activity of the stannous below this level can be put at risk. It is especially important to maintain the efficacy in compositions where the stannous binding occurs, since the binding of the stannous can easily lead to loss of antimicrobial activity. In the present, the minimal efficacy provided by the source of stannous ion is defined in terms of the effects in producing metabolic inhibition of bacterial biofilms of dental plaque, which are responsible for numerous undesirable intra-oral conditions. The efficacy is therefore defined in terms of a clear and important reduction in the in-situ plate metabolism as measured using the plaque and regrowth glycolysis model (i-PGRM), developed in the laboratories. It has been demonstrated that the i-PGRM provides an excellent correlation with the bioavailability of the stannous fluoride required to produce clinical antimicrobial, antigingivitis and antiplaque activity of oral compositions containing stannous fluoride. The efficacy of the stannous containing gingivitis compositions can be compared directly with a dentifrice containing stannous formulation such as that described in US Pat. No. 5,004,597 to Majeti, et al., And which is shown in example II below as a comparative example or with a currently marketed dentifrice containing stannous fluoride, Crest Gum Care. The i-PGRM is a technique where plaque is grown from human saliva, and treated with agents designed to produce various levels of antimicrobial activity. The purpose of this technique is to provide a simple and rapid method to determine if the compounds have a direct effect on the metabolic pathways that plaque microorganisms use for the production of toxins that adversely affect gingival health. In particular, the model focuses on the production of organic acids including lactic, acetic, propionic, and butyric. This method uses plaque cultivated in polished glass rods that have been introduced in saliva throughout the night, soy broth and sucrose for 6 hours, and again saliva throughout the night. The plaque mass cultured on the glass rods is then treated for 1 minute with a watery dentifrice paste to water 3: 1. The dough is then placed in a soy broth / sucrose solution for 6 hours and the pH of the incubation solution is measured at the end of 6 hours. Thus, there are pH measurements of previous incubation and pH after incubation for both formulations and test controls. This test is typically done with a number of duplicates to minimize the variances in the experiment, and a pH average is calculated from the duplicates. Due to the strong reactivity with saccharolytic organisms, compositions containing high levels of bioavailable stannous produce significant inhibition of plate acid generation in the i-PGRM assay. This allows variations in the formulation for stannous stability and bioavailability to be compared with relative ease. Fluorescent stannous and / or other stannous salts are found in the buccal compositions described herein in an amount effective to provide a desired i-PGRM score. The desired i-PGRM score is measured in relation to formulations that do not contain stannous (negative control) and with formulations containing stannous (positive control) such as those described in EUA 5,004,597 to Majeti et al., The scores i- Most preferred PGRMs are significantly different from placebo controls and ideally similar to those provided by conventional stannous fluoride compositions that have proven to be effective in reducing plaque and gingivitis. Research has shown that the effectiveness of effective gingivitis can be anticipated for compositions that provide at least about 60%, preferably at least about 70%, and more preferably at least about 80% of an effective dentifrice containing stannous such as the one shown in example II, comparative example, subsequently. The i-PGRM score is calculated according to the formula: (mean pH of the test product - Proportion i-PGRM = 100% x non-stannous control mean pH) (mean pH of the control of the stannous - pH of the control medium non-stannous The average pH values refer to pH incubation media obtained after treatment and sucrose problems The non-stannous control plate samples produce large amounts of acid, and therefore their pH is lower than those of the samples of plaque treated with the positive control (stable stannous fluoride dentifrice as shown in example II, comparative example) The effectiveness of a formulation prepared from the combination of a source of stannous ion and polymeric mineral surface active agent ideally it will be compared with the control that contains estanosa, and therefore the ideal i-PGRM score should approach 100%.

Reduction of staining Tooth staining is a common undesirable side effect of the use of stannous fluoride compositions. The improved stannous fluoride dentifrices described herein provide reduced dental stain formation resulting from more efficient stannous supply from stannous bound with polymeric mineral surface active agent. The staining of the surface of the teeth typically caused by the stannous is measured in the clinical situation using a spot index such as the Lobene or Meckel indexes described in the literature. The present inventors have also developed an in-vitro staining model that provides quantitative estimates for potential staining of stannous fluoride formulations that correlates well with clinical observations. The formulations can thus be tested in advance of clinical examination using these methods. The in-vitro film tea stain model (i-PTSM) is a technique where an in-vitro plate biomass is cultured on glass rods from combined human stimulated saliva over the course of three days. The plate biomass was treated with 3: 1 water to dentifrice supernatants, where the insoluble abrasive solids were removed by centrifugation, to determine the potential levels of tooth staining of the various agents. The purpose of this technique is to provide a simple and rapid method to determine if the compounds have a direct effect on the amount of dental plaque stain. This method uses plate grown in glass rods from human saliva combined with treatments of 5 minutes each, followed by a tea treatment of 10 minutes. The treatment regimen is repeated at least three times before the mass of the plate is condensed off the rods, filtered and the absorbance is measured at 380 nm. This test is typically performed with a number of duplicates to minimize the experimental variances, and a mean absorbance is calculated from the duplicates. The present invention has found that the stain that is typically produced by effective stannous fluorine is reduced by combining the stannous fluorine with one or a mixture of the polymeric mineral surface active agents discussed above. The benefit of reducing the stain caused by the stannous is achieved with the present combinations without significantly jeopardizing the efficacy of the stannous, fluorine, and polymeric surface agent. The amount of staining resulting from the buccal compositions of the present invention is significantly less than the amount of stannous resulting from typical dentifrices containing stannous. The term "reduced" as used in the present invention means a statistically significant reduction. Therefore, reducing stannous staining means that the amount of stain is statistically significantly reduced in relation to the positive control containing stannous. Not reducing the efficacy of the stannous means that the efficacy of the stannous is not statistically significantly reduced in relation to a positive control containing stannous. Alternatively, the stain can be measured in relation to typical buccal compositions that do not contain stannous fluoride or another antimicrobial agent that is known to cause staining. Therefore, the compositions can be measured in relation to very little or no stain. The i-PTSM score is calculated from this spotting test according to the formula: Score i-PTSM = 100% x Average absorbance of the test product (Mean absorbance of the control of stannous) The mean absorbance values refer to colorimetric values of digested plate obtained after dentifrice treatments and tea rinsing problems. The stannous control used is typically a highly stained, stannous fluorine formulation such as that illustrated in Example II, comparative example, later. The control plate samples produce large amounts of tea absorption and therefore increased colorimetric absorbance. In this way, the i-PTSM score is a measure of a relative level of spotting. The lower the score, the lower the level of spotting. The combination of a source of stannous ion and polymeric mineral surface active agent provides a reduction in staining and will ideally have an i-PTSM score of less than 75%, preferably less than 60%, more preferably less than 50%, mostly preferred less than 25%.

I-PGRM score ratio with i-PTSM score A key descriptor of the improvement in stannous compositions provided herein is the stannous efficacy ratio compared to the spotting potential, this being a key consumer concern. The effectiveness of the buccal composition of the present invention will be measured by a ratio of i-PGRM score to i-PTSM score. The ratio of i-PGRM score to i-PTSM score is calculated according to the formula: Ratio = score i-PGRM / score i-PTSM According to the present invention, the ratio developed using these methods should be at least about of 1.2 for important improvements in the efficacy of stannous formulation in relation to the side effects of tooth staining. The ratio is preferably greater than about 1.3, more preferably greater than about 1.5, and most preferably greater than about 2.0. If there is little to no incidence of stain, the relationship approaches infinity, which is preferred.

Stagnant binding As discussed above, the effective supply of improved stannous and stannous fluorine reactivity (efficacy with reduced side effects) requires significant in-situ binding or complexity of the stannous ion with the active mineral surface polymer (MSA). In mixed compositions containing stannous fluorine, evidence of significant stannous binding is easily observed by potentiometric detection of available ionic fluorine. For example, stannous binding with MSA polyphosphate ligand results in exchange of fluorine from stannous fluorine and release as ionic fluoride in solution. The relevant measures of stannous binding can be evaluated by this technique because fluorine is the strongest ligand in the fluoride release system is illustrative after the MSA binding agent. Thus, from the stannous union by the polymeric MSA under these conditions. The binding chemistry that occurs is illustrated in the following experiment using the dentifrice composition described in Example I in the present invention. In this experiment, the phase of the stannous fluoride / stannous cioride toothpaste (second dentifrice composition) was converted to slurry in a 1: 5 ratio with distilled water (representing a means of dilution in actual brushing). In a similar manner, a paste phase (first dentifrice composition) became slurry. This paste phase included either a (conventional) placebo dentifrice control with MSA polyphosphate or a paste phase containing 15% glass polyphosphate H according to Example I, first dentifrice formulation. The two watered pastes were mixed and ionic fluoride readings were made by fluorine electrode ISE on a digital pH meter. After reading, a standard addition of 10 and 100 fluoride excess of fold (from neutral NaF) was added to the mixed slurries allowing matrix calibration through standard addition techniques. The results shown below illustrate the stannous binding by polyphosphate as it is added to the pulp in these mixed compositions.

The results show significant and complete binding by MSA in the formulations according to this invention. It should be noted that only about 25% of the fluorine is available as fluorine ion in conventional compositions, demonstrating the strength of the stannous binding with fluorine ions. Also, the evidence of binding of stannous ion important in one-phase compositions can be demonstrated, although in these cases the binding can occur in-situ within the compositions before dilution. More importantly, stannous binding with polymeric mineral surface active agents occurs within the buccal cavity when brushing, that is, when the composition is diluted with saliva during the course of tooth brushing.

Stringency reduction Stringency is an additional side effect of many stannous containing compositions which is significantly improved in the present compositions comprising polymeric mineral surface active agents in combination with stannous and fluorine. The astringency of formulations can be measured in intra-oral panels, where the subjects evaluate the condition of the mouth before and after brushing teeth with the test formulations. In these studies, studies that depend on the time of the dentifrice effects in the subjective responses of the consumer can be carried out. In a protocol, the panelists begin a series of conditioning by cleaning the teeth with energetic proper mouth hygiene including brushing for two periods of three minutes, flossing and revealing to ensure total removal of the plaque. Subjects are then assigned their test product and instructed to brush twice a day as usual. For these tests, subjects were reported in the morning to a clinic before performing any oral hygiene or consumption of food or beverages. The panelists were then asked to fill out a subjective questionnaire to evaluate the sensation of the mouth as well as oral moisture assessments.

The panelists were then brushed for one minute with the assigned oral product. At this point, before lunch and before lunch (after noon), the subjects again filled out the subjective mouth sensation questionnaire. The results of these tests show that the present formulations containing stannous salts in combination with a polymeric mineral surface active agent such as glass polyphosphate H produce a strong improvement in formulation astringency after brushing. The astringency is reduced compared to conventional stannous formulations without the polymeric surface active agent. The acceptability of the present formulation is comparable with conventional sodium fluoride (NaF) and tartar control dentifrices respectively.

Reduction and control of calculations The provision of anticalculus benefits is another desirable aspect of the present formulations of stannous fluoride. The anticalculus activity can be predicted from measurements of activity on the mineral surface and the application of cultivated plate and mineralization tests. The present compositions include certain polymeric mineral surface active agents, such as polyphosphates that bind stannous ions. Preferred compositions contain mineral surface active phosphate polymers with significant affinity for dental surfaces, which are composed of calcium hydroxyapatites. Preferred polymeric surface active agents will include phosphate polymers that produce significant reductions in calcium phosphate mineralization as established in controlled mineralization assays. It has been discovered by the present invention that polyphosphates (in particular linear polyphosphates with average chain lengths greater than about 4) produce superior activity and substantivity to buccal surfaces compared to pyrophosphate and some other commonly used dental cleaning ingredients. The increased activity and the translation of substantivity into important improvements in the prevention of dental stains and supragingival calculus and in the non-abrasive removal of dental stains. Without wishing to be limited by theory, polyphosphates are thought to prevent the formation of supragingival calculus essentially by impairing the mineralization process, which is the formation of hard calcium phosphate mineral deposits in the enamel of the teeth. When joining the surfaces of the teeth, the polyphosphates deteriorate the process of mineral construction, because their structures do not adjust properly with the development of mineral lattice, which is converted into calcium.

Method of treatment The present invention also discloses a method for treating gingivitis and plaque with reduced staining, by using the present compositions comprising a source of stannous ion, a source of fluorine ion and particular polymeric mineral surface active agents.

Additionally, methods are provided to provide oral compositions that have benefits of cavities, gingivitis, plaque, tartar, stain, sensitivity, aesthetics, breath, mouth feel and cleanliness. The benefits of these compositions may increase over time when the composition is used repetitively. Specifically, the treatment method will include reducing gingivitis and plaque, as measured by the i-PGRM, at the same time as reducing staining caused by oral composition containing stannous, as measured by the i-PTSM. The ratio of the i-PGRM score to the score of the i-PTSM spot model is about 2. The present invention also discloses methods for reducing the dental enamel calculation incident and methods for providing the desirable buccal aesthetic benefits including reduced astringency and buccal surface conditioning effects. The benefits of these compositions may increase over time when the composition is used repetitively. Treatment methods include preparing a buccal composition containing the source of stannous ion, the source of fluorine and the polymeric mineral surface active agent and administering the composition to the subject. Administration to the subject can be defined when the oral composition contacts the surfaces of the subject's teeth when brushing with a dentifrice or rinsing with a watery dentifrice paste. Administration can also be by contacting topical mouth gel, mouthwash, dental product, mouth spray, oral tablet, pill, or chewing gum, with the surfaces of the teeth. The subject can be any person or lower animal whose surfaces of the teeth come into contact with the oral composition. It should be understood that the present invention discloses not only methods for delivering the active polymer surface active agent containing compositions to the oral cavity of a human, but also methods for delivering these compositions to the oral cavity of other animals, for example, domestic pets or other domestic animals, or animals in captivity. For example, a method of treatment may include a person who brushes the teeth of a dog with one of the dentifrice compositions. Another example will include rinsing the mouth of a cat with an oral composition for a sufficient time to observe a benefit. Pet care products such as chews and toys can be formulated to contain the oral compositions present. The composition comprising the polymeric surface active agent is incorporated in relatively soft but strong durable material such as leather, ropes made of natural or synthetic fibers, and polymeric articles made of nylon, polyester or thermoplastic polyurethane. As the animal chews, licks or gnaws the product, the incorporated active elements are released into the oral cavity of the animal in a salivary medium, comparable to effective brushing or rinsing.

Examples and methods of manufacture The following examples and descriptions further clarify the embodiments within the scope of the present invention. These examples are given for the purpose of illustration only and should not be construed as limitations of the present invention since many variations thereof are possible without departing from the spirit and scope.

EXAMPLE I Example I illustrates dual-phase dentifrice compositions that incubate sodium polyphosphate (Glass H provided by FMC Corporation, n = 21 unit of condensed phosphate polymer) in the first dentifrice composition and incorporates stannous fluoride and other stannous salts in the second composition. dentifrice First tooth compositions (a) 27.9% solution Second tooth compositions (a) 27.9% solution (b) 50% solution (c) 70% solution The first dentifrice compositions are prepared as follows: water and / or sodium laurisulfate solution and water-soluble salts are added to the main mixing vessel. In a separate container, thickeners are dispersed in glycerin. This gaseous slurry is added to the mixing vessel and mixed well. The propylene glycol and polyethylene glycol is added to the mixing vessel and mixed until well dispersed. Next, titanium dioxide and silica are added. It mixes well. The mixing vessel is cooled to less than 30 ° C and the polyphosphate is added. Mix until it becomes homogeneous. The second tooth compositions are prepared as follows: glycerin and / or sorbitol / PGE are added to the main mixing tank. Thickeners, non-ionic surfactants, flavors, stannous salts and / or fluorine salts are added to the main mix container. Mix and homogenize until it disperses well and becomes homogeneous. Water is added to the tank of the main mixture and mixed / homogenized until the salts and surfactants are dissolved, the thicknesses are hydrated and the mixture is homogeneous. Sodium hydroxide and color is added and mixed well. Sodium laurisulfate solution is added and mixed until it becomes homogeneous. The batch is cooled to less than 30 ° C. The i-PGRM scores measured, the i-PTSM scores and the i-PGRM / i-PTSM ratios are shown below for various combinations of dual phase formulations containing stannous ions, fluorine sources and polyphosphate mineral surface active agent .

EXAMPLE II Example II illustrates one-phase dentifrice compositions incorporating stannous iron salts, dispersions of suspended H glass polyphosphates or polyphosphonate polymers and various fluoride ion sources all formulated in low water base to facilitate polymeric MSA stability and stability of stannous ion. Also shown is an example of a dentifrice containing stannous as described in US Patent 5,004,597 to Majeti et al. The compositions of Example II (formula A-D below) are prepared as follows: glycerin and thickeners are added to the tank of the main mixture and mixed until it becomes homogeneous. If appropriate, add the sodium gluconate to the tank of the main mixture until it becomes homogeneous. The sodium laurisulfate and flavoring solution is added to the main mix tank and mixed until the thickeners are hydrated / dissolved. Silica and titanium dioxide are added to the main mix tank and mixed until it becomes homogeneous. Flour and / or fluorine salts are added to the tank of the main mixture and mixed until it becomes homogeneous. Finally, the polymeric surface active agent (H glass or polyphosphonate) is added to the tank of the main mixture. Mix until it becomes homogeneous. The comparative example of a dentifrice containing stannous is prepared as described in US Pat. No. 5,004,597 to Majeti, et al. Sorbitol and a medium of water are added to the tank of the mixture and heated to an initial 77 ° C. You can add saccharin, titanium dioxide and silica to the mixture during this period of heating. Sufficient agitation is maintained to avoid deposit of the insoluble compounds. The glycerin is added to a separate container and it is also heated to 77 ° C. When both solutions have reached the required temperature, carboxymethylcellulose (CMC) is slowly added to the glycerin under vigorous stirring. When CMC has been sufficiently dispersed in the glycerin, the mixture is added to the sorbitol / water mixture. The resulting mixture is then combined for a sufficient period to allow total hydration of the binders (approximately 15 minutes). When the paste has the acceptable texture, the flavoring, the sodium alkyl sulfate and the color are added. Then a medium of the remaining water is added to a separate mixing tank and allowed to run at 77 ° C. After the water reaches the necessary temperature, the sodium gluconate is added under medium stirring and allowed to dissolve completely. The stannous chloride dihydrate is then added to the gluconate solution and allowed to dissolve. This mixture is added to the main mix. The stannous fluoride is added to the remaining water (also at 77 ° C) and the resulting solution is added to the main mixture and allowed to combine perfectly before the final pH adjustment with the sodium hydroxide. The finished paste is stirred for approximately 20 minutes before grinding and desing (a) solution at 27.9% (b) solution at 50% (c) solution at 1% (d) solution at 70%

Claims

NOVELTY OF THE INVENTION CLAIMS 1. - A buccal composition having effective antimicrobial activity to reduce plaque and gingivitis, said composition comprising: a) a source of stannous ion; b) a source of fluorine ion; and c) a polymer surface active agent, whereby said polymer surface active agent combines stannous ions and is fundamental to mineral surfaces. 2. The oral composition according to claim 1, which has reduced staining and reduced astringency. 3. The oral composition according to claim 1, further characterized in that the source of stannous ion supplies stannous ions of about 3,000 ppm to about 15,000 ppm. 4. The oral composition according to claim 1, further characterized in that the source of fluorine ion has the capacity to provide fluorine ions of about 50 ppm to 3500 ppm. 5. The oral composition according to claim 1, further characterized in that the polymer surface active agent is from about 1% to about 35%. 6. The oral composition according to claim 5, further characterized in that the mineral surface active agent is a phosphorylated polymer. 7. The oral composition according to claim 6, further characterized in that the phosphorylated polymer is a condensed polyphosphate having a chain length of about 4 or more. 8. The oral composition according to claim 1, further characterized in that the source of fluorine ion comprises stannous fluorine. 9. The oral composition according to claim 8, further characterized in that the stannous source comprises a combination of stannous fluorine and stannous chloride dihydrate. 10. The oral composition in accordance with the claim 8, which also comprises a gluconate salt. 11. The oral composition according to claim 7, further characterized in that the molar ratio of phosphate anion to the stannous ion is from about 0.2: 1 to about 5: 1. 12. The oral composition in accordance with the claim 7, further characterized in that the condensed phosphate polymer is glass H. 13.- The buccal composition according to claim 1, further characterized in that the source of stannous ion and the source of fluorine ion are physically separated from the surface active agent. polymeric 14. The oral composition according to claim 1, further characterized in that the score ratio of the plaque glysis model and in-vitro regrowth with the score of the in-vitro film tea stain model at least about 1.2. . 15. The oral composition according to claim 1, further characterized in that the score of the model of glysis of plaque and regrowth in-vitro is at least about 60%, preferably at least about 70%, and with greater preference at least around 80%. 16.- The oral composition in accordance with the claim 1, further characterized in that the scoring of the in-vitro film tea stain model is at least about 75%, preferably less than 60%, more preferably less than 50%, most preferably less than 25% 17. The oral composition according to claim 1, further characterized the buccal composition is essentially free of alkali metal pyrophosphate salt. 18.- The oral formulation in accordance with the claim 1, further characterized the buccal composition additionally comprises a poloxamer. 19. A method for effectively reducing plaque and gingivitis in a subject without increasing the staining of teeth comprising administering to said subject a composition comprising: a) a source of stannous ion; b) a source of fluorine ion; and c) a polymer surface active agent, whereby said polymer surface active agent combines stannous ions and is fundamental to mineral surfaces. 20. - A buccal composition comprising: a) a first composition comprising a source of fluorine ion and a source of stannous ion; b) a second composition comprising a linear polyphosphate having an average chain length of about 4 or more, whereby the composition has a total water content of up to about 20%; whereby said polyphosphate binds the stannous ions to the intra-oral contact of the first composition and second composition. 21. The oral composition in accordance with the claim 20, further characterized in that the first composition has a total water content of about 5% to about 95%. 22. The oral composition in accordance with the claim 21, further characterized in that the second composition contains a glossy abrasive material.